The applicant is interested in control mechanisms of hemoglobin synthesis at the molecular level, particularly as it applies to human disease. In the present proposal; the objective is to define requirements for optimal hemoglobin synthesis in the human reticulocyte and the effect of maturation on the cells' ability to form polyribosomes, in vitro. This investigation will also be directed towards an understanding of the molecular defects in thalassemia and hemoglobinopathies. Blood will be obtained from patients by venepuncture in an antecubital vein, using aseptic techniques. We estimate that between 20 to 100 ml of blood will be collected from each patient. Nothing will be injected into these patients, nor will any medications, isotopes or any other substances be given. This study is entirely in vitro and human will be used solely as a source of erythrocytes with the only procedure involving them being venepuncture.